Influence of salidroside, a neuroactive compound of Rhodiola rosea L., on alcohol tolerance development in rats

Abstract

SummaryIntroduction: In recent years, the search for potential neuroprotective properties of salidroside and its ability to influence the activity of nervous system become the subject of intense studies of many research groups. None of these studies, however, include an attempt to determine the effect of salidroside on the course of alcohol tolerancein vivo.Objective: The aim of this study was to investigate the ability of salidroside to inhibit the development of alcohol tolerance in rats, determining whether the effect of its action may occur in a dose-dependent manner, reducing both metabolic and central tolerance without affecting body temperature in control rats.Methods: Male Wistar rats were injected daily with ethanol at a dose of 3 g/kg for 9 consecutive days to produce ethanol tolerance. Salidroside in two doses (4.5 mg/kg and 45 mg/kgb.w.) orvehiculumwas administered orally. On the 1st, 3rd, 5th and 8th day a hypothermic effect of ethanol was measured, while the loss of righting reflex procedure was performed on the 2nd, 4th, 6th and 7th day. On the 9th day rats were treated with salidroside, sacrificed 1 h after ethanol injections and blood was collected for blood-ethanol concentration measurement.Results: Salidroside at a dose of 45 mg/kg inhibited the development of tolerance to hypothermic and sedative effects of ethanol, whereas insignificant elevation of blood-ethanol concentration was observed. The dose of 4.5 mg/kgb.w.had minimal effect, only small inhibition of tolerance to hypothermic action was observed. Salidroside affected neither body mass growth nor body temperature in non-alcoholic (control) rats.Conclusions: Results of the study indicate that salidroside at a dose of 45 mg/kg inhibited the development of tolerance to the hypothermic effect of ethanol. Observed inhibition of tolerance to the sedative effect of ethanol seems to be associated with salidroside influence on the central nervous system. A comprehensive explanation of the abovementioned observations requires further pharmacological and pharmacodynamic studies.

Lack of salidroside impact on selected cytochromes encoding genes transcription in the liver of ethanol induced rats

“…In the course of these studies, the inhibition of the development of tolerance to hypothermic and sedative effects of ethanol in RR-treated rats [11] as well as in Sal-administered rodents (45 mg/kg b. w.; p.o.) was observed, which, in both cases, was accompanied by an increase in the peripheral level of ethanol [11,12]. These observations gave rise to the assumption that this compound may potentially have an inhibitory effect on the metabolic level.…”

“…and 45 mg/kg b.w., p.o. ), which induced tolerance to the presence of a high dose of ethanol [12]. Also, in relation to the above-mentioned two studies, an attempt was made to almost directly measure the change in the molecular activities of CYPs under the influence of Sal and EtOH using a different research technique -the quantitative PCR with real-time detection of changes in fluorescence gain.…”

“…The experiment was approved by the Local Ethics Committee for Animal Experiments (consent number: 87/2015). A detailed description of the in vivo experiment was previously described by Szulc et al [12]. After completion of the experiment, the right hepatic lobe was removed from each animal immediately after decapitation and secured in liquid nitrogen for molecular analysis.…”

“…In recent years, the potential of inhibiting the development of alcohol tolerance by Rhodiola rosea L. (RR) and Rhodiola kirilowii (Regel) Maxim (RK) root extracts [11] and the key active metabolite contained in these extracts -salidroside (Sal) [12], belonging to the representatives of phenylethanoid glycosides [13], has been demonstrated. In the course of these studies, the inhibition of the development of tolerance to hypothermic and sedative effects of ethanol in RR-treated rats [11] as well as in Sal-administered rodents (45 mg/kg b. w.; p.o.)…”

Ethnopharmacological Applications Targeting Alcohol Abuse: Overview and Outlook

“…Rhodiola (golden root) Salidroside Male Wistar rats Indicates that salidroside at a dose of 45 mg/kg inhibited the development of tolerance to the hypothermic effect of (Szulc et al, 2018) ethanol. Observed inhibition of tolerance to the sedative effect of ethanol seems to be associated with salidroside influence on the CNS.…”